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大约20%～40%的乳腺癌患者化疗后可出现记忆力、注意力、思维等大脑认知功能减退，又称化疗脑，可能持续至康复期并干扰日常生活技能和生活质量。化疗脑一旦发生以后，亡羊补牢比较困难，故有必要未雨绸缪、防患未然，在化疗前预测化疗后有脑功能减退风险的乳腺癌患者，将有助于改善患者治疗，例如有针对性地进行早期干预，减少或避免采用蒽环类等神经毒性化疗药物。 2021年9月30日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表荷兰国家癌症研究所、阿姆斯特丹大学的研究报告，探讨了乳腺癌化疗后大脑认知功能减退的风险因素和预测方法。 该单中心病例对照研究对乳腺癌患者接受蒽环类化疗前（52例）和化疗后6个月（49例）、2年（32例）和3年（32例）进行神经心理问卷评分和脑磁共振检查，以匹配的时间间隔对乳腺癌未化疗患者（39例、39例、23例、19例）和无癌症对照者（44例、37例、29例、28例）进行神经心理问卷评分和脑磁共振检查。通过多因素规范化比较，对患者组与对照组的认知特征偏差程度进行分析。根据磁共振弥散张量成像的各向异性分数，对治疗前的脑白质微观结构进行定量。除了基线年龄、疲劳、认知主诉和病前智商之外，各向异性分数被评价为认知能力下降的风险因素。随后，进行体素弥散张量成像分析，分析特定神经束的脑白质微观结构。 结果发现，脑磁共振弥散张量成像的各向异性分数可独立预测乳腺癌患者化疗后早期（6个月，P=0.013）和晚期（3年，P<0.001）认知能力减退，与年龄、病前智商、基线疲劳和基线认知主诉无关，而且不能预测乳腺癌未化疗患者和无癌症对照者的认知能力减退。体素分析表明，脑白质束对认知功能至关重要。 因此，该单中心小样本研究结果表明，乳腺癌化疗前脑磁共振弥散张量成像的各向异性分数可能反映脑白质储备，可能是乳腺癌化疗后认知能力减退的风险因素。对脑白质储备较低的患者进行化疗前筛查，将有助于改善患者治疗，例如促进有针对性的早期干预，甚至影响患者和医生对化疗药物的选择，故有必要进一步开展多中心大样本研究进行验证。 J Clin Oncol. 2021 Sep 30. Online ahead of print. Brain White Matter Microstructure as a Risk Factor for Cognitive Decline After Chemotherapy for Breast Cancer. de Ruiter MB, Reneman L, Kieffer JM, Oldenburg HSA, Schagen SB. Netherlands Cancer Institute, Amsterdam, the Netherlands; University of Amsterdam, Amsterdam, the Netherlands. PURPOSE: Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy. METHODS: Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts. RESULTS: Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning. CONCLUSION: Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy. KEY OBJECTIVE: Is magnetic resonance imaging-based brain white matter microstructure before chemotherapy for breast cancer a risk factor for cognitive decline after chemotherapy? KNOWLEDGE GENERATED: A low fractional anisotropy, reflecting white matter microstructure, predicted cognitive decline 6 months and 3 years after chemotherapy, independent of age, premorbid intelligence quotient, baseline fatigue, and baseline cognitive complaints. RELEVANCE: Low fractional anisotropy may reflect low white matter reserve, putting a patient at risk for chemotherapy-associated cognitive decline. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy. PMID: 34591652 DOI: 10.1200/JCO.21.00627
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